We plan to continue our investigation of the function of the subunits of F1 ATPase, the energy transducing ATPase or coupling factor of E. coli. To this end we shall isolate the alpha, beta and gamma subunits in a homogeneous state and determine their role in catalysis and in the association of this important enzyme. Later, we want to purify the membrane component, F, and to reconstitute oxidative phosphorylation in artificial vesicles. We plan to use the methods that we have developed to isolate the subunits of ATPase from mutant strains, as a help in elucidating function. In other studies we plan to isolate the carrier protein for the D-lactate or the gluconate transport systems of E. coli, which we believe to be favorable for study. We shall continue our studies on energy coupling, especially the role of ATP in energizing active transport for shock-sensitive systems. We plan to investigate the mechanism whereby ATP increases the permeability of transformed mammalian cells and also the mechanism by which this change is reversed. We shall explore ways in which this phenomenon can be put to use, to introduce drugs or biologically active nucleic acids into such "permeabilized" cells. BIBLIOGRAPHIC REFERENCES: Smith, J.B., Sternweis, P.C. and Heppel, L.A. "Partial purification of active delta and epsilon subunits of the membrane ATPase from Escherichia coli (1975) J. Supramolecular Structure 3:248-255. Rozengurt, E. and Heppel, L.A. "Stimulation of Rb transport in quiescent mouse fibroblast cultures by serum" 1975. Proc. Nat. Acad. Sci. USA 72: 1581.